59 articles - From Saturday Feb 05 2022 to Friday Feb 11 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
meta-analyses and systematic reviews
| J Hematol Oncol |
Serologic response following SARS-COV2 vaccination in patients with cancer: a systematic review and meta-analysis. Patients with cancer, especially those with hematologic B-cell malignancies, have a lower serologic response to COVID-19 vaccines. The results suggest that cancer patients should continue to follow safety measures including mask-wearing after vaccination and suggest the need for additional strategies for prophylaxis. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Optimizing the Diagnostic Workflow for Acute Lymphoblastic Leukemia by Optical Genome Mapping. OGM also provided opportunities for better patient stratification and accurate treatment options. However for comprehensive cytogenomic testing, OGM still needs to be complemented with CBA or SNP-array to detect ploidy changes and with BCR::ABL1 FISH to assign patients as soon as possible to targeted therapy. |
Phase 2 studies of lenalidomide, subcutaneous bortezomib, and dexamethasone as induction therapy in patients with newly diagnosed multiple myeloma. The most common toxicity was peripheral neuropathy (pooled: 68%, 7% grade 3-4; CTI study: 57%, 7%; DFCI study: 79%, 7%). Proteomics analyses indicated elevated kallikrein-6 in good versus poor responders, decreased midkine in good responders, and elevated macrophage inflammatory protein 1-alpha in patients who stopped treatment from neurotoxicity, suggesting predictive biomarkers warranting further investigation. |
Pregnancy Outcomes with Hydroxyurea Use in Women with Sickle Cell Disease. In analyses of live birth outcomes, hydroxyurea use during conception and pregnancy was associated with birth weight <5.5 pounds in full-term infants (OR 2.98, 95% CI 1.09-7.38) but not with prematurity or serious medical problems at birth. These findings suggest that hydroxyurea use may be safe up to the time of conception, but that clinicians should continue to advise caution regarding use during pregnancy. |
| Ann Oncol |
Biomarkers of treatment benefit with atezolizumab plus vemurafenib plus cobimetinib in BRAFV600 mutation-positive melanoma. Treatment benefits in the atezolizumab group seemed to be most evident in patients with elevated LDH and PD-L1- tumors. LDH remains the primary predictor of outcomes regardless of treatment. IFN- |
First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology. |
| Blood |
Donor-Derived Multiple Leukemia Antigen Specific T-cell Therapy to Prevent Relapse Post-Transplant in Patients with ALL. Thus, this approach represents a promising strategy to prevent relapse in ALL patients. Clinical trial is registered under NCT02475707 at clinicaltrials. gov. |
How I treat refractory/relapsed hairy cell leukemia with BRAF inhibitors. These include patients with, or at risk of, severe infections and, in a highly effective combination with rituximab, patients with relapsed or refractory HCL. Other treatments explored in clinical trials are BTK inhibition with ibrutinib and co-inhibition of BRAF (through dabrafenib or vemurafenib) and its downstream target MEK (through trametinib or cobimetinib). Here, we focus on our experience with BRAF inhibitors in clinical trials and as off-label use in routine practice by presenting three challenging clinical cases to illustrate their management in the context of al available treatment options. |
Selective inhibition of activated protein C anticoagulant activity protects against hemophilic arthropathy. Administration of MAPC1591, and not MPC1609, markedly reduced the severity of HA. MAPC1591 inhibited joint-bleed induced inflammatory cytokine IL-6 expression and vascular leakage in joints, whereas MPC1609 had no significant effect. Our data show that a mAb that selectively inhibits APC's anticoagulant activity without compromising its cytoprotective signaling offers a therapeutic potential alternative to treat HA. |
Single Cell Transcriptional Analysis of Human Endothelial Colony Forming Cells from Patients with Low VWF Levels. A siRNA screen of potential VWF modifiers provided further evidence of regulatory candidates, and one such candidate, FLI1, alters the transcriptional activity of VWF. In conclusion, ECFCs from Low VWF individuals demonstrate alterations in their baseline VWF packaging and release as compared to control ECs. scRNA-seq revealed alterations in VWF transcription and siRNA screening identified multiple candidate regulators of VWF. |
Targeting macrophages for enhancing CD47 blockade-elicited lymphoma clearance and overcoming tumor-induced suppression. In addition, we identified a role of paclitaxel in modifying the TME by preventing the accumulation of a TAM subpopulation that is only present in late-stage lymphoma resistant to CD47-targeted therapy. Our findings identify a novel and effective strategy for NHL treatment, by remodeling TME to enable the tumoricidal roles of TAMs. Furthermore, we characterize TAM subgroups that determine the efficiency of lymphoma phagocytosis in the TME and can be potential therapeutic targets to unleash the anti-tumor activities of macrophages. |
Telomeres, aging, and cancer: the big picture. The goal of this perspective is to summarize some of these observations and to discuss the antagonistic role of telomere loss in aging and cancer in the context of developmental biology, cell turnover, and evolution. It is proposed that both damage to DNA and replicative loss of telomeric DNA contribute to aging in humans, with the differences in leukocyte telomere length between humans being linked to the risk of developing specific diseases. These ideas are captured in the Telomere Erosion in Disposable Soma theory of aging proposed herein. |
Unbiased cell surface proteomics identifies SEMA4A as an effective immunotherapy target for myeloma. Using knock-down by shRNA and CRISPR/dCas9, we demonstrate that expression of SEMA4A is essential for normal myeloma cell growth in vitro, indicating that myeloma cells cannot downregulate the protein to avoid detection. We further show that SEMA4A would not be identified as a myeloma therapeutic target by standard CRISPR/Cas9 knockout screens because of exon skipping. Finally, we potently and selectively targeted SEMA4A with a novel antibody-drug conjugate in vitro and in vivo. |
| Blood Adv |
4-1BBL-containing leukemic extracellular vesicles promote immunosuppressive effector regulatory T cells. Finally, we showed that costimulatory ligand 4-1BBL/CD137L, shuttled by leukemic EVs, promoted suppressive activity and effector phenotype of Tregs by regulating expression of receptors such as CD30 and TNFR2. Collectively, our work highlights the role of leukemic extracellular vesicles in stimulation of immunosuppressive regulatory T cells and leukemia growth. We postulate that targeting of Rab27a-dependent secretion of leukemic EVs may be a viable therapeutic approach in myeloid neoplasms. |
A biomarker panel for risk of early respiratory failure following hematopoietic cell transplantation. Using cause-specific landmark analysis including days 7 and 14, high plasma ST2, WFDC2, IL6, and TNFR1 values were associated with increased HR for RF in the training and validation cohorts. These biomarkers were also predictive of mortality with RF. ST2, WFDC2, IL6 and TNFR1 levels measured early post-transplantation improve risk stratification for RF and its related mortality. |
A Prognostic Model to Predict Survival After 6 Months of Ruxolitinib in Patients with Myelofibrosis. Hence, we developed a prognostic model, named Response to Ruxolitinib after 6 months (RR6), dissecting three risk categories: low (median OS not reached), intermediate (median OS 61 months, 95% CI 43-80), and high (median OS 33 months, 95% CI 21-50). The RR6 model was validated and confirmed in an external cohort comprised of 40 MF patients. In conclusion, the RR6 prognostic model allows for the early identification of RUX-treated MF patients with impaired survival who might benefit from a prompt treatment shift. |
Circulating primitive murine erythroblasts undergo complex proteomic and metabolomic changes during terminal maturation. Increased expression of several antioxidant enzymes also indicates modification to redox homeostasis. In addition, accumulation of oxylipins and cholesteryl esters in primitive OrthoE cells was paralleled by increased transcript levels of the p53-regulated cholesterol transporter (ABCA1) and decreased transcript levels of cholesterol synthetic enzymes. The present study characterizes the extensive metabolic rewiring that occurs in primary embryonic erythroid precursors as they prepare to enucleate and continue circulating without internal organelles. |
Circulating Tumor DNA Predicts Therapeutic Outcome in Mantle Cell Lymphoma. Monitoring ctDNA after induction showed that molecular relapse can precede clinical relapse in some cases. In conclusion, interim ctDNA negativity strongly correlates with improved survival and supports the investigation of response-adapted strategies. |
Fludarabine Exposure Predicts Outcome after CD19 CAR T-Cell Therapy in Children and Young Adults with Acute Leukemia. In the underexposed group, the median leukemia-free survival was 1.8 months and the occurrence of CD19-positive relapse within 1 year was 100%, which was higher compared to the group with an AUCT0-8 =14 mg*h/L (12.9 months; p<.001 and 27.4%; p=.0001, respectively). Furthermore, the duration of B cell aplasia within 6 months was shorter in the underexposed group (77.3% versus 37.3%; p=.009). These results suggest that optimizing fludarabine exposure may have a relevant impact on leukemia-free survival following CAR T cell therapy, which needs to be validated in a prospective clinical trial. |
G6b-B regulates an essential step in megakaryocyte maturation. RNA sequencing revealed a striking global reduction in the level of megakaryocyte-specific transcripts, in conjunction with decreased protein levels of the transcription factor GATA-1, and impaired thrombopoietin signaling. The reduced number of mature MKs in the bone marrow was corroborated on a newly developed Mpig6b null mouse strain. Our findings highlight an unexpected essential role of G6b-B in the early differentiation within the megakaryocytic lineage. |
GRNDaD: big data and sickle cell disease. sicklecellcenters. org/). GRNDaD is a robust collaborative registry that providers and researchers will use to identify genetic markers that will help predict outcomes and lead to a better understanding of the natural history of SCD in the modern era of novel therapies. |
Hematological malignancies magnify the effect of body mass index on insulin resistance in cancer survivors. This interaction also remained significant after adjusting for log IL-6 (P-interaction=0.048) and log MCP-1 (P-interaction=0.021). Cancer survivors have disproportionately greater insulin resistance with increasing BMI compared to controls without malignancy. The effect modification between cancer and BMI in determining insulin sensitivity implicates cancer-specific etiologies in glucose dysregulation and could partially explain excess diabetes diagnoses among oncology patients. |
Historical expectations with DNMTI monotherapy in MDS: When is combination therapy truly 'promising'? CR rates were similar between DNMTIs: 13% with azacitidine and 16% with decitabine. Variables that influence MDS response include the specific DNMTI backbone and the distribution of IPSS risk of patients enrolled on a trial. Considering these factors can help identify which early combination approaches are worth assessing in larger randomized trials. |
Molecular profile of FLT3-mutated relapsed/refractory AML patients in the phase 3 ADMIRAL study of gilteritinib. However, the occurrence of Ras/MAPK pathway gene mutations at baseline did not preclude a clinical benefit from gilteritinib. Acquisition of multiple Ras/MAPK pathway gene mutations at relapse suggests a high level of pathway reactivation is needed to overcome the gilteritinib treatment effect. These findings provide insight into the R/R AML molecular profile and the impact of FLT3 inhibitors on mutational evolution associated with treatment resistance and benefit of gilteritinib across a wide spectrum of molecular and genetic subgroups in FLT3-mutated R/R AML. |
| CA Cancer J Clin |
Cancer statistics for African American/Black People 2022. The wide breast cancer disparity reflects both later stage diagnosis (57% localized stage vs 67% in White women) and lower 5-year survival overall (82% vs 92%, respectively) and for every stage of disease (eg, 20% vs 30%, respectively, for distant stage). Breast cancer surpassed lung cancer as the leading cause of cancer death among Black women in 2019. Targeted interventions are needed to reduce stark cancer inequalities in the Black community. |
| Haematologica |
A novel CD34-specific T-cell engager efficiently depletes acute myeloid leukemia and leukemic stem cells in vitro and in vivo. Additionally, the BiTE triggered efficient T-cell-mediated depletion of CD34+ HSCs from peripheral blood stem cell grafts and CD34+ blasts from AML patients. Using a humanized AML xenograft model, we confirmed that the CD34-specific BiTE had in vivo efficacy by depleting CD34+ blasts and LSCs without side effects. Taken together, these data demonstrate robust antitumor effects of the CD34-specific BiTE supporting development of a novel treatment modality with the aim of improving outcomes of patients with AML and myelodysplastic syndromes. |
A pilot study of the use of dynamic cfDNA from aqueous humor and vitreous fluid for the diagnosis and treatment monitoring of vitreoretinal lymphomas. The objective response rate of ibrutinib treatment was much higher for PCNSL patients (64.7%, 11/17) than VRL (14.3%, 1/7) patients. In summary, we provided valuable clinical evidence that AH is a good source of tumor genomic information and can be substituted for VF. Moreover, molecular profiling of AH has clinical utility for the diagnosis of VRL and treatment monitoring. |
CCR6 activation links innate immune responses to MALT lymphoma development. While in the gastric setting, HBD2, and HD5, to a less extent CCL20, were highly expressed in epithelial cells of pyloric and intestinal metaplasia respectively including those involved in LELS, which are adaptive responses to chronic H pylori infection. These findings suggest that CCR6 signaling is most likely active in MALT lymphoma, independent of its mutation status. The observations explain why the emergence of malignant Bcells and their clonal expansion in MALT lymphoma are typically around LELs, linking the innate immune responses to lymphoma genesis. |
Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and BCR-ABL positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin. Allo-HCT evaluated as a time-dependent variable had no impact on OS. INO seems to be effective as debulking strategy in r/r-ALL with EMD. However, INO followed by allo-HCT seems not to be effective in maintaining long term disease control. |
Proline-rich tyrosine kinase Pyk2 regulates deep vein thrombosis. Finally, we found that expression of Pyk2 was required for NETosis induced by activated platelets. Altogether our results demonstrate a critical role of Pyk2 in the regulation of the coordinated thromboinflammatory responses of endothelial cells, leukocytes and platelets leading to venous thrombosis. Pyk2 may represent a novel promising target in the treatment of deep vein thrombosis. |
The impact of aberrant von Willebrand factor-GPIba interaction on megakaryopoiesis and platelets in humanized type 2B von Willebrand disease model mouse. Moreover, altered megakaryocyte (MK) maturation in the bone marrow and enhanced extramedullary megakaryopoiesis in the spleen were observed. Interestingly, injection of anti-VWF A1 blocking antibody (NMC-4) not only ameliorated platelet count and GPIba expression, but also reversed MK ploidy shift. In conclusion, we present a type 2B VWD mouse model with humanized VWF-GPIba interaction which demonstrated direct influence of aberrant VWFGPIba binding on MKs. |
| Leukemia |
Genetic correlates in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with Hyper-CVAD plus dasatinib or ponatinib. IKZF1 deletion frequently co-occurred with other copy-number abnormalities (IKZF1 plus , 46%) and was significantly associated with unfavorable overall survival (OS) (false discovery rate |
| Thromb Haemost |
Adjusting D-dimer to lung disease extent to exclude Pulmonary Embolism in COVID-19 patients (Co-LEAD). Using the Co-LEAD algorithm, 76/250 (30.4%) COVID-19 patients with suspected PE could have been managed without CT pulmonary angiography (CTPA). The Co-LEAD algorithm safely excludes PE, and allows reducing the use of CTPA among COVID-19 patients. Further prospective studies are necessary to validate this strategy. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
| Blood |
| J Hematol Oncol |
Designing strategies of small-molecule compounds for modulating non-coding RNAs in cancer therapy. Thus, in this review, we focus on summarizing some new emerging designing strategies, such as high-throughput screening approach, small-molecule microarray approach, structure-based designing approach, phenotypic screening approach, fragment-based designing approach, and pharmacological validation approach. Based on the above-mentioned approaches, a series of representative small-molecule compounds, including Bisphenol-A, Mitoxantrone and Enoxacin have been demonstrated to modulate or selectively target ncRNAs in different types of human cancers. Collectively, these inspiring findings would provide a clue on developing more novel avenues for pharmacological modulations of ncRNAs with small-molecule drugs for future cancer therapeutics. |
Functions, mechanisms, and therapeutic implications of METTL14 in human cancer. To date, the molecular mechanism of METTL14 in various malignant tumors has not been fully studied. In this paper, we systematically summarize the latest research progress on METTL14 as a new biomarker for cancer diagnosis and its biological function in human tumors and discuss its potential clinical application. This study aims to provide new ideas for targeted therapy and improved prognoses in cancer. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| J Hematol Oncol |
The global landscape of neoadjuvant and adjuvant anti-PD-1/PD-L1 clinical trials. The confirmatory neoadjuvant trials were particularly insufficient, and the combination strategy mainly focused on chemotherapy. Thus, more public funding and accelerated regulatory strategies are needed in this field. Efforts should be made to confirm the benefit of neoadjuvant treatment and explore novel combination strategies. |
| Leukemia |
all remaining publications eg case reports, images of the month, etc…
| Blood |
| Blood Adv |
| Leukemia |
| Thromb Haemost |